Sequential Allogeneic Stem Cell Transplantation in High Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome

Aim:  To evaluate this strategy in high risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

We treated 17 patients with AML or MDS. This cohort consisted of nine patients who did not reach complete remission, 5 patients who reached complete remission but remained  with high burden of residual disease and 3 patients up front transplanted for myelodysplatic syndrome with high blast count. Median age was 54 years (32-65years).  Median count of blasts in bone marrow before sequential transplantation was 9% (1-76%). 6 patients were transplanted with HLA identical sibling, 8 patients were transplanted with matched unrelated donor (10/10) and 3 patients had unrelated donor with one mismatch (9/10). Flag-Ida chemotherapy (CHT) (n=4), 3+7 CHT (n=7) or CHT based on monotherapy with Cytarabin was used as a cytoreduction. Between cytoreductive CHT and preparative regimen was instituted rest period with median of 5 days (2-14 days).  After these days of rest preparative regimen consisted of Fludarabin/Busulfan was initiated. Total dose o Busulfan was 8mg/kg n=6), 12mg/kg(n=6) nad 16mg/kg (n=5). Thymoglobulin (total dose 7,5mg/kg) was used in case of unrelated donor in days -3 to -1.

Results: Estimated overall survival at 2 years was 67,6%. Whole regimen was tolerated very well even with the highest dose of Busulfan. Transplant related mortality at 100 days  was 6% (1 patient with insufitient engraftment died due to infection).  5 patients relapsed after transplantation, 1 patient progressed after transplantation. From these patients just 1 patient did not die due to relapse and was succesfully rescued with chemotherapy and donor lymphocyte infusion.

Conclusion: Sequential transplantation is our method of choice in high risk AML and MDS. We demonstrate very low transplant related mortality and promising long term survival of this cohort of high risk patients.